How are primitive neuroectodermal tumors (PNETs) treated?

Updated: Feb 07, 2019
  • Author: Carlo P Honrado, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Chemotherapy and radiation are necessary adjuncts in the treatment of primitive neuroectodermal tumors (PNETs). Chemotherapy regimens have significantly improved outcomes in patients with peripheral primitive neuroectodermal tumors (pPNETs). The treatment paradigms differ based on whether the disease is localized or metastatic. As would be expected, the treatments for peripheral primitive neuroectodermal tumors (pPNETs) and Ewing family of tumors (EFTs) are similar in terms of chemotherapeutic regimens.

Current recommendations advocate complete surgical resection whenever possible, adjuvant versus neoadjuvant chemotherapy, and radiotherapy. Multimodality treatment is advocated to prevent metastatic disease, recurrent disease, and to treat residual tumor after resection. Carvajal and Meyers, in a comprehensive review of the chemotherapeutic regimens in the treatment of PNETs and Ewing family of tumors (EFTs), recommend a regimen that includes vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide (IE). [24]

The treatment of metastatic disease similarly includes neoadjuvant and adjuvant chemotherapy, as well as radiotherapy to all sites of gross disease with surgical excision, where possible. As there is a paucity of head and neck peripheral primitive neuroectodermal tumors (pPNETs) reported in the literature, clinical trials for treatment regimens specific to the head and neck is limited. Current treatment strategies and response rates often include tumors from other subsites. Recommendations for fractionated treatment schedules with higher treatment doses are typically reserved for patients with gross residual disease and microscopic disease.

A mitigating factor in the adjuvant use of radiotherapy is the known complication of a second sarcoma that develops subsequent to treatment with radiation. In addition, treatment-related acute myeloblastic leukemia and myeloblastic syndrome occur in 1-2% of survivors of EFT. In childhood cancer survivors followed through the SEER cancer registries, the greatest risk of subsequent cancers occurred among those previously diagnosed with EFT and PNETs, nearly a 6-fold increase compared to the general population. [25] The incidence of secondary malignancies increases substantially with radiotherapy treatment doses of more than 60 Gy. Kuttesch et al reported that 20% of patients who receive doses of more than 60 Gy developed secondary malignancies, compared with only 5% in those who receive 48-60 Gy. Those treated with less than 48 Gy had no additional risk of second malignancies. [26]

While outcomes vary based on disease subsite, patients with metastatic disease uniformly have poor outcome ranging from 0-25% 5-yr survival rates compared to 40-79% for those with localized disease. [27]

A retrospective study by Jin et al indicated that thyroid dysfunction is common in children with either primitive neuroectodermal tumor (PNET) or pediatric medulloblastoma (a cerebellar PNET). The study group consisted of 56 patients with medulloblastoma and 10 patients with PNET, all children. By a median 3.8 years follow-up, transient hypothyroidism had developed in 12 patients (18%), and permanent hypothyroidism had arisen in 37 (56%). Analysis demonstrated that radiation exposure at age less than 5 years and patient exposure to high-dose chemotherapy are risk factors for hypothyroidism in pediatric patients with medulloblastoma or PNET. [28]

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